Splanchnic Nerve Block for Therapy of Chronic Heart Failure (Splanchnic III)

Chronic Heart Failure Clinical Trial

Official title:

Splanchnic Nerve Block for Therapy of Chronic Heart Failure (Splanchnic III)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04575428
• Other study ID #: Pro00103788
• Status: Completed
• Phase: Phase 2
• Start date: February 5, 2020
• Est. completion date: June 16, 2021

Study information

• Verified date: May 2023
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Splanchnic vasoconstriction may contribute to decompensation of chronic heart failure (HF) via volume redistribution from the splanchnic vascular bed to the central compartment. This is a sympathetically mediated reflex and can be interrupted through a splanchnic nerve block (SNB). We hypothesize that interruption of the efferent/afferent innervation of the splanchnic vasculature will decrease cardiac congestion in patients presenting with HF. Based on preliminary safety and efficacy data in acute and chronic heart failure patients with temporary (<24 h) SNB. Now we will apply a prolonged SNB in chronic heart failure patients using a long acting agent. We will test the effects of SNB on long term exercise capacitance.

Description:

Activation of splanchnic nerves results in vasoconstriction and reduces splanchnic capacitance, therefore recruiting blood volume into the central circulation. In heart failure, a reduced splanchnic vascular capacitance could be the mechanism underlying symptoms of exercise intolerance and could predispose to rapid decompensation with external fluid intake or retention. A compromised vascular reservoir is likely unable to buffer shifts of fluid and actively contributes to the acute or chronic expulsion of fluid from the splanchnic vascular compartment to the central thoracic compartment. The redistribution of blood volume into the central circulation may lead to a sudden rise in pulmonary and left-sided cardiac pressures in HF. This makes the splanchnic vascular compartment an attractive target in heart failure. Our preliminary proof-of-concept work in patients with acute decompensated and chronic heart failure showed promise for the concept of splanchnic nerve modulation in heart failure. In a series of two small first-in-human studies for acute decompensated heart failure (N=13) (NCT02669407) and chronic heart failure (N=17) (NCT03453151), we found that a splanchnic nerve block (SNB) with lidocaine (90 min duration of action) and ropivacaine (24 hours duration of action) acutely reduced resting and exercise-induced intra-cardiac filling pressures, associated with improved patient symptoms and functional capacity.

The present study will be a prospective open-label pilot study to help establish feasibility, safety and enable dose finding for botulinumtoxin. Following a baseline invasive (right heart catheterization) cardiopulmonary exercise testing (CPX) patients will undergo unilateral celiac plexus block, followed by repeat hemodynamic testing. Functional testing at baseline and follow up will be supplemented by measures of blood volume and autonomic tone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: June 16, 2021
• Est. primary completion date: June 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Followed at DUMC for known or suspected diagnosis of HF (NYHA stage 2-4, Class C-D), including patients on inotropic medication

• Systolic blood pressure (SBP) > 100 mmHg

• History of HF hospitalization or ER visit or iv diuretic use in last 12 months.

• Patients will be included regardless of left ventricular ejection fraction.

Exclusion Criteria:

• Anticoagulation at the time the procedure or in case of recent warfarin use an INR >1.4. Anticoagulation includes: warfarin, or novel oral anticoagulants like dabigatran, rivaroxaban, apixaban, endoxaban or full dose intravenous heparin products or bivalirudin and fondaparinux). Antiplatelet agents besides aspirin such as ticagrelor, prasugrel, Plavix are also considered to be a contraindication if used at time point of procedure.

• Immunosuppressive medications for solid organ transplant

• Acute MI (STEMI or Type I NSTEMI) within 7 days?

• Evidence of progressive cardiogenic shock within 48 hours

• Restrictive cardiomyopathy

• Constrictive pericarditis

• Pericardial effusion with evidence of tamponade

• Severe valvular stenosis requiring intervention

• Known history of an increased bleeding risk

• Thrombocytopenia (< 50,000)

• End-stage renal disease CKD stage 5 due to primary renal pathology

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Drug:
• Splanchnic nerve block
Percutaneous splanchnic nerve block

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak Exercise Wedge Pressure	Measured with cardiopulmonary exercise testing	4 weeks
Primary	Peak Pulmonary Arterial Pressure	Measured on exercise cardiopulmonary stress test	4 weeks
Primary	Absence of Nerve Block Related Complications	Assessment of orthostasis, gastrointestinal symptoms were observed	8 weeks
Secondary	Peak Oxygen Uptake		4 weeks
Secondary	Resting Wedge Pressure	Assessed with right heart cath	4 weeks
Secondary	Resting Central Venous Pressure	Assessed with right heart cath	4 weeks
Secondary	Resting Pulmonary Arterial Pressure	Assessed on right heart catheterization	4 weeks
Secondary	Dyspnea - Visual Analog Scale (VAS)	The VAS for dyspnea has a range of 0 to 100, where 0 corresponds to the patient's subjective feeling of "I Can Breathe Normally" and a score of 100 corresponds to "I Can't Breathe At All."	4 weeks